The overall goal is to elucidate themetabolic pathways involving condensation reactions of neuronal catecholamines (CAs) during chronic alcohol abuse. The syntheses of various isoquinolines which are related structurally to L-DOPA and CAs, particularly epinephrine and norepinephrine, are being continued. The pure substances are being studied for their effects on brain and peripheral tissue monoamine levels and histopathology. The metabolic routes of O-methylation and oxidation of isoquinolines are being clarified. The possible production of the condensation products in vivo during alcoholic states is being studied using rodents. Highly sensitive and specific chromatographic (capillary GC with electron capture; HPLC) techniques being utilized for these studies.